To assess whether oral vaccination against human papillomavirus (HPV) may be feasible, we administered HPV virus-like particles (VLPs) to mice by gavage. Enzyme-linked immunosorbent assay (ELISA) results indicated that serum anti-VLP immunoglobulin G (IgG) and IgA antibodies were induced after oral vaccination, and these responses demonstrated antigenic specificities that were conformationally dependent and restricted according to HPV genotype. Importantly, orally induced postimmune sera were found to neutralize HPV-11 virions in vitro. These results indicated that the VLPs were antigenically stable in the environment of the gastrointestinal tract and were able to engage in potentially useful immune system interactions. These findings support the concept of oral vaccination against anogenital HPV disease, and suggest the possibility that this may be a useful approach to the immunization of large populations against cervical cancer and other HPV associated diseases.